Dibenz azepines, oxidation

Similar problems arise with the four isomeric dibenzazepines 4-7. since only 5//-dibenz-[6,d]azepine (4) and 5//-dibenz[/>,./]azepine (7) can be drawn as fully benzenoid ring structures. Even so, 5//-dibenz[/ ,t/]azepines are rare and are known only as the 7-oxo derivatives.4 In contrast, 5//-dibenz[6,e azepine (5) and 6//-dibenz[r,t>]azepine (6) exist only as the 11//- 5a and 5H- 6a isomers, respectively. In fact, there is no chemical or spectrosopic evidence for the isomerization of 5//-dibenz[e,e]azepine,5 or its 6-oxide,6 to the 6//-dibenz[r, e]azcpinc isomer (6). In addition, an X-ray crystal structure of 7-methoxy-5//-dibenz[e,e]azepine supports unequivocally the benzenoid rather than the quinonoid form.7 9//-Tribenz[6,d /]azepine (8) has only recently been prepared.8... 

Nitroso-5//-dibenz[/>,/]azepine (9, R = NO) is relatively stable to photolysis under argon, whereas in benzene solution in the presence of oxygen, irradiation induces an oxidative Fischer -Hepp-type rearrangement to 2-nitro-5//-dibenz[6,/]azepinc (10, R = N02), accompanied by ring contraction to acridine-9-carbaldehyde184 (see also Section 3.2.2.4.). 

Low yields of the 5-acetyl-l0,11-epoxy derivative 11 (R = Me) are also obtained by oxidation of 5-acetyl-5//-dibenz[/>,/]azepine (10, R = Me) with iodoxybenzene and vanadium(lll) acetylacetonate, and with iodosobenzene and iron(lll) porphyrin.220... 

Dihydroacridine-10-carbaldehyde (4) is the major product (57%) from the oxidation of 1 l//-dibenz[7),e]azepine (3) with peracetic acid.222 1 l//-Dibenz[/),e,]azcpin-6(5/7)-one (5) is also formed along with trace amounts ( < 4 %) of 9-acridone-10-carbaldehydeand 5,6-dihydro-l 1H-dibenz[ >,< ]azepine-6,l 1-dionc. 

Dialkyl-5//-dibenz[/>,/]azepines 6 on oxidation with 3-chloroperoxybenzoic acid undergo ring contraction to 9,10-dihydroacridinc-9-carbaldehydes 7.223 In contrast, 5,10,11-trialkyl derivatives 8 yield mixtures of the acridinyl ketones 9 and 10,11-epoxides 10. 

Dibenz[6, e]azepines conformation, 7, 499 11H-Dibenz[6,e]azepines oxidation, 7, 525 reduction, 7, 517 synthesis, 7, 532, 533 Dibenz[6,/]azepines JV-acyl derivatives UV spectra conformation, 7, 499 mass spectrum, 7, 501 nitroxide... 

Grignard reagent, 7, 514 5H-Dibenz[6,/]azepine, 3-chloro-10,l 1-dihydro-oxidation, 7, 525... 

H-Dibenz[c,e]azepine, N-alkyl-6,7-dihydro-oxidation, 7, 511 6H-Dibenz[c,e]azepine, dihydroconformation, 7, 499... 

Bromo-6-ethoxy-7//-dibenz[/>,d]azepin-7-one(28, R1 = OEt Rz = Br). prepared by oxidation of the 5,6-dihydro derivative 27 with manganese(IV) oxide, is one of the few examples of unsaturated dibenz[/>,d]azepines to be reported.4 Earlier reports concerning the preparation of the parent system 28 (R = R2 = H) are incorrect the product is in fact a dimer.115... 

A detailed study of the dehydrogenation of 10.1 l-dihydro-5//-benz[6,/]azcpinc (47) over metal oxides at 550 C revealed that cobalt(II) oxide, iron(III) oxide and manganese(III) oxide are effective catalysts (yields 30-40%), but formation of 5//-dibenz[7),/]azepinc (48) is accompanied by ring contraction of the dihydro compound to 9-methylacridine and acridine in 3-20 % yield.111 In contrast, tin(IV) oxide, zinc(II) oxide. chromium(III) oxide, cerium(IV) oxide and magnesium oxide arc less-effective catalysts (7-14% yield) but provide pure 5H-dibenz[b,/]azepine. On the basis of these results, optimum conditions (83 88% selectivity 94-98 % yield) for the formation of the dibenzazepine are proposed which employ a K2CO,/ Mn203/Sn02/Mg0 catalyst (1 7 3 10) at 550 C. 

Dibenz[c,e]azepine 6-oxide (4, R = H) has been prepared in high yield (95 %) by oxidation of the cyclic hydroxainic acid 3 (R = H) with mercury(II) oxide.6 Oxidation of the unsym-metrically substituted derivative 3 (R = Ph) is regiospecific and yields only 5-phenyl-5//-dibenz[e,e]azepine 6-oxide (4, R = Ph 60% mp 188-189 C). 

Unlike the parent system, 5-methyl-5//-dibenz[c,e]azepine (1, R1 = Me R2 = H) on treatment with lithium diisopropyl amide fails to yield the tautomeric phenanthridine-imine (see Section 3.2.1.5.4.2.), but forms the 5-carbanion, which on quenching with deuterium oxide furnishes 5-methyl-[5-2H,]-5//-dibenz[e,e]azepine (l).83 5,7-Diphenyl-5//-dibenz[r,e]azepine (1. R1 = R2 = Ph) behaves similarly. In contrast, however, 5,7-dimethyl-5//-dibcnz[c,e]azepine (1, R1 = R2 = Me) yields theazaallyl anion 3, which on addition of deuterium oxide deuterates regiospecifically at the 7-methyl group to give derivative 4. 

Prolonged treatment (20 h) of 5//-dibenz[6,/]azepine (5, R1 = H) with an excess of butyllithium, followed by quenching into deuterium oxide, furnishes [4,6-2H2]-5//-dibcnz[6,/]azepine (rap 195-197 C) in 93% yield.47... 

Amino-77/-dibenz[/),t/]azepin-7-ones, e.g. 7, prepared either by successive bromination, aminodebromination, and dehydrogenation of 5-tosyl-5A/-dihydro 7>,t/]azepin-7(6//)-ones, or by the oxidation of 6-ethoxy-6,7-dihydro-5//-dibenz 7>,r/]azepincs with lead(IV) acetate followed by aminodemethoxylation, on treatment with a bidentate nucleophile (e.g.. benzene-1,2-diamine or 2-aminobenzenethiol) yield the pentacyclic systems 8 and 9, respectively.27... 

Generation of the anion of 5,7-diphenyl-5//-dibenz[c,e]azepine (6) under phase-transfer conditions in the presence of air results in oxidation and formation of the dibenz[c,c]azepinol 7 whose structure was confirmed by X-ray crystallography.85... 

Oxidation of 6-aryl-5//-dibenz[c e]azepinium bromides, e.g. 8, with hydrogen peroxide results in formation of bis(6-phenyl-6,7-dihydro-5//-dibenz[c.e ]azepin-7-yl)peroxide (9).92... 

Acyl-lO.l l-epoxy-5//-dibenz[6,/]azepines 11 are obtained in moderate yields by oxidation of 5-acyl-5//-dibenz[A,/]azepines 10 with 3-chloroperoxybenzoic acid124 197,219 (see also Section 3.2.2.2.2.). As expected, peracid oxidation of 10-(alkylsulfanyl)-5//-dibenz[A,/]azepincs occurs at sulfur rather than at the CIO —Cl 1 double bond.213... 

Oxidation of 5//-dibenz[7>,/]azepine (12) with Fremy s salt [ON(S03K)2] yields a mixture of acridine-9-carbaldehyde (13) and 2//-dibenz[A,/]azepin-2-one (14).215 The dibenzazepin-2-one 14 is also obtained in 46% yield with bis(trifluoroacetoxy)pentafluoroiodobenzene [PhI(OCOCF3)2] in acetonitrile as the oxidant.221... 

Acridine-9-carbaldehyde (24%) is one of several products formed from the oxidation of 5//-dibenz[A/]azepine with tert-butyl hypochlorite in dichloromethane at — 70 C.229 The reaction is even more complex in the presence of silver(I) trifluoroacetate, and an analysis of the reaction mixture by GC-MS techniques reveals the presence of eleven products, the major ones being acridine (37%), an unidentified 5//-dibenz[/ ,/]azepinecarbaldehyde (23%) and acridine-9-carbaldehyde (9 %). 

Phenylmagnesium bromide adds to the imine bond of 5//-dibenz[c,< ]azepine 6-oxide to yield 5-phenyl-6,7-dihydro-5//-dibenz[ce]azepin-6-ol (mp 171 —172°C).6... 

Dibenz[c,e]azepine 6-oxide, a cyclic nitrone (see Section 3.2.1.5.1.), yields crystalline 1,3-dipolar cycloadducts with phenylisocyanate (adduct yield 98 % mp 190-191 C) and with N-phenylmaleimide (adduct yield 86% mp 235-236°C).6... 

There are only a few reports concerning the peracid oxidation of azepines. 30% Hydrogen peroxide oxidizes TV-alkyl-6,7-dihydro-5iT-dibenz[c,e]azepines to their TV-oxides (75ZN(B)926), whereas MCPBA has been used to prepare the 3H-2-benzazepine TV-oxide (88) (74JOC2031). TV-Oxidation of 2,3,4,5-tetrahydro-lH-l-benzazepine with MCPBA is accompanied by dehydrogenation to the 4,5-dihydro TV-oxide (89) (79JOC4213). 

The oxidation of AT-substituted 5//-dibenz[6,/] azepines with MCPBA is complex and depends upon the nature of the N-substituent. AT-Acyl derivatives do not form the N-oxide but suffer epoxidation of the 10,11-bond. AT-Aryl derivatives undergo hydroxylation of the phenyl ring, whereas N-alkyl congeners, with the exception of the AT-methyl compound, yield mixtures of diphenylamines and acridones. The N-oxide is obtained from the A/-methyl derivative along with ring-opened and ring-contracted products (81CPB1221). 

The electrochemical oxidation of 5//-dibenz[6,/]azepine and related compounds has been investigated (75MI51600). 

The 1,3-dipolar nitrone character of dibenz[c,e]azepine N-oxide (161) is apparent in its cycloadditions with phenyl isocyanate, JV-phenylmaleimide (74ZN(B)425> and JV-sulfinylaryl-sulfonamides (ArS02NS0) (81TL2141). 

Oxidation of 5//-dibenz[6,/]azepines by Fremy s salt has been examined closely. At pH 7.5 the quinonoid dibenz[6,/]azepin-2-one is produced together with acridine-9-aldehyde (74CRV101). 3-Chloro-10,11 -dihydro-5//-dibenz[6,/]azepine yields a mixture of the quinoneimines (174 R=C1) and (175) which with sodium dithionite reduce to the corresponding chlorohydroxydihydrodibenzazepines (76JHC269). 

Oxidation of 1 l//-dibenz[6,< ]azepine with peracetic acid yields the dibenzazepin-6-one and N-formylacridan as the major products. Both products most probably result from an oxaziridine intermediate (76JCS(Pi)l29l). 

Calculations by the Pariser-Parr-Pople method on the quinoneimine obtained by Fremy s salt oxidation of dibenz[6,/]azepine indicate that the carbon adjacent to the carbonyl group is the most nucleophilic center. This is confirmed by nitration [Cu(N03)2-Ac0H] and bromination [NBS-(PhC0)202] studies, in which the 1-substituted derivatives are obtained. However, acylation by Vilsmeier or Friedel-Crafts reaction fails, extensive decomposition of the ring system taking place. 

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